PHOX2A

Summary

PHOX2A (paired like homeobox 2A, HGNC:691) is a protein-coding gene on chromosome 11q13.4, encoding Paired mesoderm homeobox protein 2A (O14813). May be involved in regulating the specificity of expression of the catecholamine biosynthetic genes.

The protein encoded by this gene contains a paired-like homeodomain most similar to that of the Drosophila aristaless gene product. The encoded protein plays a central role in development of the autonomic nervous system. It regulates the expression of tyrosine hydroxylase and dopamine beta-hydroxylase, two catecholaminergic biosynthetic enzymes essential for the differentiation and maintenance of the noradrenergic neurotransmitter phenotype. The encoded protein has also been shown to regulate transcription of the alpha3 nicotinic acetylcholine receptor gene. Mutations in this gene have been associated with autosomal recessive congenital fibrosis of the extraocular muscles.

Source: NCBI Gene 401 — RefSeq curated summary.

At a glance

• Gene–disease (curated): fibrosis of extraocular muscles, congenital, 2 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 36 total — 2 pathogenic
• Phenotypes (HPO): 43
• Transcription factor: yes — 14 downstream targets (CollecTRI)
• MANE Select transcript: NM_005169

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:691
Approved symbol	PHOX2A
Name	paired like homeobox 2A
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	PMX2A, CFEOM2
Ensembl gene	ENSG00000165462
Ensembl biotype	protein_coding
OMIM	602753
Entrez	401

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000298231, ENST00000544057, ENST00000546310

RefSeq mRNA: 4 — MANE Select: NM_005169 NM_001425096, NM_001425097, NM_001425098, NM_005169

CCDS: CCDS8214

Canonical transcript exons

ENST00000298231 — 3 exons

Exon	Start	End
ENSE00001093262	72243788	72244176
ENSE00001093264	72239077	72240198
ENSE00003553384	72241102	72241289

Expression profiles

Bgee: expression breadth broad, 68 present calls, max score 82.15.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8524 / max 1509.0707, expressed in 148 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121157	1.8236	142
121152	0.0118	5
121156	0.0072	2
121153	0.0060	3
121154	0.0039	2

Top tissues by expression

257 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.69	gold quality
parotid gland	UBERON:0001831	78.21	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	71.36	gold quality
tongue squamous epithelium	UBERON:0006919	69.77	gold quality
oocyte	CL:0000023	66.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	66.12	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	65.10	gold quality
biceps brachii	UBERON:0001507	64.99	gold quality
mammary duct	UBERON:0001765	63.22	gold quality
vena cava	UBERON:0004087	62.64	gold quality
pericardium	UBERON:0002407	62.37	silver quality
epithelium of mammary gland	UBERON:0003244	62.34	gold quality
caecum	UBERON:0001153	62.20	gold quality
vermiform appendix	UBERON:0001154	62.09	gold quality
mucosa of urinary bladder	UBERON:0001259	61.91	gold quality
superficial temporal artery	UBERON:0001614	61.88	gold quality
orbitofrontal cortex	UBERON:0004167	61.88	gold quality
synovial joint	UBERON:0002217	61.68	gold quality
vastus lateralis	UBERON:0001379	61.58	gold quality
quadriceps femoris	UBERON:0001377	61.44	gold quality
tendon of biceps brachii	UBERON:0008188	61.39	gold quality
hair follicle	UBERON:0002073	61.16	gold quality
pharyngeal mucosa	UBERON:0000355	60.83	gold quality
trabecular bone tissue	UBERON:0002483	60.60	gold quality
heart right ventricle	UBERON:0002080	60.58	gold quality
cartilage tissue	UBERON:0002418	60.49	gold quality
cervix squamous epithelium	UBERON:0006922	60.46	gold quality
mammalian vulva	UBERON:0000997	60.34	gold quality
tongue	UBERON:0001723	60.32	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	1063.06
E-ANND-3	no	0.40

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

14 targets.

Target	Regulation
CDKN1B	Unknown
CHRNA3
DBH	Activation
GATA2
HAND1
NCAM1	Unknown
NRXN1
PHOX2A
PHOX2B
PRKACA
RET	Activation
SLC6A2	Activation
TH
TLX2	Activation

JASPAR motifs

Motif	Name	Family
MA0713.1	PHOX2A	Paired-related HD factors

JASPAR matrix evidence (PMIDs): PMID:18585360

Upstream regulators (CollecTRI, top): ASCL1, CREB1, HAND2, PAX3, PHOX2A, PHOX2B, TLX2

miRNA regulators (miRDB)

39 targeting PHOX2A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-6529-3P	98.68	66.76	1020
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-676-5P	98.49	68.87	1492

Literature-anchored findings (GeneRIF, showing 19)

• Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy (PMID:11889467)
• The paired-like homeodomain protein, Arix, mediates protein kinase A-stimulated dopamine beta-hydroxylase gene transcription through its phosphorylation status (PMID:11943777)
• PHOX2A mutation analysis revealed a novel nonsense mutation in CFEOM2 (congenital fibrosis of extraocular muscles type 2) (PMID:14597037)
• the polymorphisms of the ARIX gene and PHOX2B gene may be genetic risk factors for the development of congenital superior oblique muscle palsy (PMID:16049556)
• PHOX2A, but not PHOX2B, seems to act directly on the c-RET promoter (PMID:16127999)
• Together, these results suggest that phosphorylation of Arix by ERK1/2 inhibits its ability to interact with target genes, and that both specificity of expression and modulation by external stimuli are monitored through the same transcription factor. (PMID:16156742)
• These results demonstrate the direct interactions of the Phox2a and b and dHAND transcription factors within a noradrenergic cell type (PMID:16280598)
• the alpha3 subunit is expressed in every terminally differentiated ganglionic cell, this is the first example of a “pan-autonomic” gene whose expression is regulated by PHOX2 proteins. (PMID:17344216)
• PHOX2A, like PHOX2B, is involved in the cascade leading to transcription factor TLX2 transactivation and presumably is involved in intestinal neuronal differentiation. (PMID:17505528)
• a variant of Secretogranin II has a role in regulation by PHOX2 transcription factors and in hypertension (PMID:17584765)
• The ARIX 153G>A polymorphism might be a genetic risk factor for the development of congenital superior oblique muscle palsy (PMID:18323871)
• PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma. (PMID:18949361)
• PHOX2A gene, localized in a tumor suppressor candidate region at 11q, weas screened for mutations by DNA sequencing in 47 tumors of different stages. (PMID:19212675)
• Transfection of Phox2a cDNA significantly increases mRNA and protein levels of norepinephrine transporter and dopamine beta-hydroxylase. (PMID:19573018)
• Our 16-patient sample suggests that KIF21A and PHOX2A sequence variation does not have a role in common forms of congenital incomitant vertical strabismus. (PMID:19852579)
• Patients with ARIX and/or PHOX2B polymorphisms had less hypoplastic superior oblique muscles. (PMID:22170461)
• Genetic linkage was found at 11q13 between D11S4151 and D11S1320 and the PHOX2A gene. (PMID:22311481)
• PHOX2A expression is finely controlled during retinoic acid differentiation and this, together with PHOX2B down-regulation. (PMID:26902400)
• Outcomes of strabismus surgery in genetically confirmed congenital fibrosis of the extraocular muscles. (PMID:31541710)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	phox2a	ENSDARG00000007406
mus_musculus	Phox2a	ENSMUSG00000007946
rattus_norvegicus	Phox2a	ENSRNOG00000019706
caenorhabditis_elegans	ceh-17	WBGENE00000440

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), PAX7 (ENSG00000009709), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), RHOXF1 (ENSG00000101883), CRX (ENSG00000105392), EVX1 (ENSG00000106038), PAX4 (ENSG00000106331), NOBOX (ENSG00000106410), PITX3 (ENSG00000107859), PHOX2B (ENSG00000109132), OTX1 (ENSG00000115507), PRRX1 (ENSG00000116132), VSX2 (ENSG00000119614), ESX1 (ENSG00000123576), PAX8 (ENSG00000125618), PAX1 (ENSG00000125813), RHOXF2 (ENSG00000131721), GSC (ENSG00000133937), RAX (ENSG00000134438), PAX3 (ENSG00000135903), ALX3 (ENSG00000156150), HESX1 (ENSG00000163666), PITX2 (ENSG00000164093), UNCX (ENSG00000164853), OTX2 (ENSG00000165588), DRGX (ENSG00000165606), PRRX2 (ENSG00000167157), SHOX2 (ENSG00000168779), OTP (ENSG00000171540), RAX2 (ENSG00000173976), EVX2 (ENSG00000174279), PROP1 (ENSG00000175325), ISX (ENSG00000175329), ALX1 (ENSG00000180318), MIXL1 (ENSG00000185155), SHOX (ENSG00000185960)

Protein

Protein identifiers

Paired mesoderm homeobox protein 2A — O14813 (reviewed: O14813)

Alternative names: ARIX1 homeodomain protein, Aristaless homeobox protein homolog, Paired-like homeobox 2A

All UniProt accessions (2): O14813, H0YGU5

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in regulating the specificity of expression of the catecholamine biosynthetic genes. Acts as a transcription activator/factor. Could maintain the noradrenergic phenotype.

Subcellular location. Nucleus.

Disease relevance. Fibrosis of extraocular muscles, congenital, 2 (CFEOM2) [MIM:602078] A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 2 may result from the defective development of the oculomotor (nIII), trochlear (nIV) and abducens (nVI) cranial nerve nuclei. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the paired homeobox family.

RefSeq proteins (4): NP_001412025, NP_001412026, NP_001412027, NP_005160* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR050649	Paired_Homeobox_TFs	Family

Pfam: PF00046

UniProt features (9 total): compositionally biased region 3, sequence variant 2, chain 1, DNA-binding region 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14813-F1	64.49	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 186 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, DORSAM_HOXA9_TARGETS_UP, SP3_Q3, GOBP_NEUROGENESIS, GOBP_CRANIAL_NERVE_MORPHOGENESIS, GOBP_CRANIAL_NERVE_DEVELOPMENT, chr11q13, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD, SP1_Q2_01, GOBP_SPINAL_CORD_MOTOR_NEURON_DIFFERENTIATION, GOBP_VENTRAL_SPINAL_CORD_DEVELOPMENT

GO Biological Process (14): noradrenergic neuron differentiation (GO:0003357), regulation of transcription by RNA polymerase II (GO:0006357), somatic motor neuron differentiation (GO:0021523), oculomotor nerve formation (GO:0021623), trochlear nerve formation (GO:0021642), locus ceruleus development (GO:0021703), midbrain development (GO:0030901), regulation of respiratory gaseous exchange (GO:0043576), positive regulation of transcription by RNA polymerase II (GO:0045944), sympathetic nervous system development (GO:0048485), neuron development (GO:0048666), dopaminergic neuron differentiation (GO:0071542), regulation of DNA-templated transcription (GO:0006355), parasympathetic nervous system development (GO:0048486)

GO Molecular Function (7): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron differentiation	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
cranial nerve formation	2
regulation of transcription by RNA polymerase II	2
autonomic nervous system development	2
system development	2
transcription cis-regulatory region binding	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
spinal cord motor neuron differentiation	1
oculomotor nerve morphogenesis	1
trochlear nerve morphogenesis	1
pons development	1
neural nucleus development	1
brain development	1
anatomical structure development	1
respiratory gaseous exchange by respiratory system	1
regulation of multicellular organismal process	1
positive regulation of DNA-templated transcription	1
cell development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

730 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PHOX2A	KIF21A	Q7Z4S6	960
PHOX2A	ASCL1	P50553	877
PHOX2A	DBH	P09172	861
PHOX2A	TUBB3	Q13509	815
PHOX2A	TH	P07101	714
PHOX2A	HAND2	P61296	709
PHOX2A	ISL1	P20663	687
PHOX2A	NR2F6	P10588	673
PHOX2A	GDNF	P39905	650
PHOX2A	INPPL1	O15357	648
PHOX2A	EDN3	P14138	634
PHOX2A	RET	P07949	606
PHOX2A	INSM1	Q01101	539
PHOX2A	MKS1	Q9NXB0	492
PHOX2A	GATA2	P23769	464

IntAct

13 interactions, top by confidence:

A	B	Type	Score
PHOX2A	DNM2	psi-mi:“MI:0915”(physical association)	0.560
	PHOX2A	psi-mi:“MI:0915”(physical association)	0.560
PHOX2A	PRPH	psi-mi:“MI:0915”(physical association)	0.560
PHOX2A	HTRA2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (8): PHOX2A (Affinity Capture-MS), HAND2 (Reconstituted Complex), JUN (Reconstituted Complex), PHOX2A (Affinity Capture-Western), PHOX2A (Two-hybrid), PHOX2A (Reconstituted Complex), SP1 (Affinity Capture-Western), PHOX2A (Affinity Capture-Western)

ESM2 similar proteins: A0A1W2PQ73, A1YF16, A1YG93, A2RU54, A5PKG8, O02786, O14813, O15353, O35602, O43638, O57601, P13297, P19419, P28360, P35548, P41969, P42580, P43687, P49640, P50223, P50548, P52946, P52950, P63156, P63157, P70459, P78413, Q03358, Q14549, Q2VL78, Q2VL79, Q2VL82, Q2VL83, Q2VL84, Q2VL85, Q2VL86, Q2VL87, Q2VL88, Q5NSW5, Q61575

Diamond homologs: A0A1W2PPK0, A0A1W2PPM1, A1A546, A1YEY5, A1YFI3, A1YG57, A1YGA2, A2T733, A2T777, A2T7P4, A6NFQ7, G5EC89, L8E946, O14813, O15499, O35690, O42250, O42356, O42357, O42477, O70137, O73917, O75360, O95076, O97670, P0DMV5, P26367, P26630, P29454, P41935, P47237, P47238, P53544, P53545, P53546, P54366, P55813, P55864, P56915, P56916

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKACA	down-regulates	PHOX2A	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

36 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	26
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
6838	NM_005169.4(PHOX2A):c.217+1G>A	Pathogenic
6839	NM_005169.4(PHOX2A):c.406-1G>A	Pathogenic

SpliceAI

520 predictions. Top by Δscore:

Variant	Effect	Δscore
11:72241099:CA:C	donor_loss	1.0000
11:72241100:A:AC	donor_gain	1.0000
11:72241101:C:CC	donor_gain	1.0000
11:72241101:C:T	donor_loss	1.0000
11:72241101:CCTG:C	donor_gain	1.0000
11:72241296:G:C	acceptor_gain	1.0000
11:72241298:G:GC	acceptor_gain	1.0000
11:72241300:G:C	acceptor_gain	1.0000
11:72241300:G:GC	acceptor_gain	1.0000
11:72241312:C:CT	acceptor_gain	1.0000
11:72241312:C:T	acceptor_gain	1.0000
11:72241313:G:T	acceptor_gain	1.0000
11:72240194:CAGAC:C	acceptor_gain	0.9900
11:72240198:CCTG:C	acceptor_loss	0.9900
11:72240199:CT:C	acceptor_loss	0.9900
11:72240200:T:G	acceptor_loss	0.9900
11:72241100:ACCTG:A	donor_gain	0.9900
11:72241101:CCTGC:C	donor_gain	0.9900
11:72241285:GGGCA:G	acceptor_gain	0.9900
11:72241286:GGCA:G	acceptor_gain	0.9900
11:72241287:GCA:G	acceptor_gain	0.9900
11:72241288:CA:C	acceptor_gain	0.9900
11:72241288:CAC:C	acceptor_gain	0.9900
11:72241290:C:CC	acceptor_gain	0.9900
11:72241293:CGGG:C	acceptor_gain	0.9900
11:72241296:G:GC	acceptor_gain	0.9900
11:72241298:G:C	acceptor_gain	0.9900
11:72241303:C:CT	acceptor_gain	0.9900
11:72241304:A:T	acceptor_gain	0.9900
11:72243782:GCTCA:G	donor_loss	0.9900

AlphaMissense

1807 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:72240163:T:A	K147N	1.000
11:72240163:T:G	K147N	1.000
11:72240164:T:A	K147I	1.000
11:72240165:T:C	K147E	1.000
11:72240168:G:A	R146C	1.000
11:72240168:G:C	R146G	1.000
11:72240168:G:T	R146S	1.000
11:72240169:G:C	F145L	1.000
11:72240169:G:T	F145L	1.000
11:72240170:A:G	F145S	1.000
11:72240171:A:G	F145L	1.000
11:72240172:C:A	K144N	1.000
11:72240172:C:G	K144N	1.000
11:72240173:T:A	K144M	1.000
11:72240174:T:C	K144E	1.000
11:72240176:G:A	A143V	1.000
11:72240176:G:T	A143D	1.000
11:72240177:C:G	A143P	1.000
11:72240179:C:G	R142P	1.000
11:72240179:C:T	R142Q	1.000
11:72240180:G:A	R142W	1.000
11:72240180:G:C	R142G	1.000
11:72240182:C:A	R141L	1.000
11:72240182:C:G	R141P	1.000
11:72240183:G:A	R141C	1.000
11:72240183:G:C	R141G	1.000
11:72240183:G:T	R141S	1.000
11:72240184:G:C	N140K	1.000
11:72240184:G:T	N140K	1.000
11:72240185:T:A	N140I	1.000

dbSNP variants (sampled 300 via entrez): RS1000006533 (11:72245809 C>A,T), RS1000090569 (11:72239655 T>A), RS1000579399 (11:72244513 G>A), RS1000657278 (11:72246021 C>T), RS1001545408 (11:72238735 C>A), RS1001944802 (11:72244189 G>A,C,T), RS1002077406 (11:72243763 A>C,T), RS1002589694 (11:72241673 G>A,T), RS1003133918 (11:72241465 G>C), RS1003352972 (11:72242922 C>T), RS1003429384 (11:72241221 T>C), RS1003875483 (11:72243246 T>C), RS1004153662 (11:72242186 C>T), RS1004154644 (11:72243824 C>A), RS1004228856 (11:72244136 C>G,T)

Disease associations

OMIM: gene MIM:602753 | disease phenotypes: MIM:602078

GenCC curated gene-disease

Disease	Classification	Inheritance
fibrosis of extraocular muscles, congenital, 2	Strong	Autosomal recessive
congenital fibrosis of extraocular muscles	Supportive	Autosomal dominant

Mondo (2): fibrosis of extraocular muscles, congenital, 2 (MONDO:0011181), congenital fibrosis of extraocular muscles (MONDO:0007614)

Orphanet (0):

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000044	Hypogonadotropic hypogonadism
HP:0000473	Torticollis
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000539	Abnormality of refraction
HP:0000542	Impaired ocular adduction
HP:0000565	Esotropia
HP:0000577	Exotropia
HP:0000609	Optic nerve hypoplasia
HP:0000616	Miosis
HP:0000646	Amblyopia
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001357	Plagiocephaly
HP:0001477	Compensatory chin elevation
HP:0001488	Bilateral ptosis
HP:0001491	Congenital fibrosis of extraocular muscles
HP:0002013	Vomiting
HP:0002126	Polymicrogyria
HP:0002194	Delayed gross motor development
HP:0003577	Congenital onset
HP:0007831	Nonprogressive restrictive external ophthalmoplegia
HP:0007936	Restrictive external ophthalmoplegia
HP:0008527	Congenital sensorineural hearing impairment
HP:0009380	Finger aplasia
HP:0009916	Anisocoria

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C566587	Fibrosis Of Extraocular Muscles, Congenital, 2 (supp.)
C580012	congenital fibrosis of the extraocular muscles (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
terbufos	increases methylation	1
sodium arsenite	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
bisphenol S	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Antirheumatic Agents	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies